It is the purpose of this project to develop an in vitro assay system which could be used for the rapid determination of the toxicity of retinoids which, in turn, could be used to gain insight into the mechanism of action of retinoid toxicity. Such information could be used to rationally develop new retinoids with increased biological activity in the reversal of preneoplastic lesions in epithelial tissue but at the same time have decreased toxicological activity.